Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials
Autor: | John R. Mascola, Lily Zhang, Logashvari Naidoo, Erica Lazarus, David P. Burns, Myron S. Cohen, Michal Juraska, Yunda Huang, Lindsay N. Carpp, Kathryn Therese. Mngadi, Pedro Gonzales, April K. Randhawa, Julie E. Ledgerwood, Margarita M. Gomez Lorenzo, Allan C. deCamp, Nyaradzo Mgodi, Erika Rudnicki, Srilatha Edupuganti, Adrian B. McDermott, Shelly Karuna, Peter B. Gilbert, Philip Andrew, Lawrence Corey |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Adult
Male 0301 basic medicine Anti-HIV Agents Human immunodeficiency virus (HIV) Physiology lcsh:Medicine HIV Infections HIV Antibodies medicine.disease_cause General Biochemistry Genetics and Molecular Biology Neutralization VRC01 Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Neutralization Tests Broadly neutralising antibodies medicine Humans Population pharmacokinetics Antibody mediated prevention trials Volume of distribution lcsh:R5-920 biology business.industry lcsh:R Hiv incidence Antibodies Monoclonal General Medicine Middle Aged Antibodies Neutralizing Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis Cohort Mixed effects biology.protein HIV-1 Female Drug Monitoring Antibody business lcsh:Medicine (General) Broadly Neutralizing Antibodies Research Paper |
Zdroj: | EBioMedicine, Vol 64, Iss, Pp 103203-(2021) EBioMedicine |
ISSN: | 2352-3964 |
Popis: | The phase 2b AMP trials are testing whether the broadly neutralising antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modelling of longitudinal serum VRC01 concentrations to characterise pharmacokinetics and predict HIV-1 neutralisation coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralisation coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralisation coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralisation correlate with HIV incidence. |
Databáze: | OpenAIRE |
Externí odkaz: |